To the Editor.—I am concerned that the study by Dr Maizels et al, which shows efficacy for intranasal lidocaine in the treatment of migraine headaches, is a demonstration of the ability of therapy to show a positive response rate when the treatment and placebo are not equivalent. This is an important issue regarding this double-blind randomized controlled study, because intranasal lidocaine is highly irritative and can easily be distinguished from the relatively benign and comfortable instillation of saline that was used as a control. It is reasonable to expect that the treatment that causes more irritation might cause a higher placebo response rate, as has been demonstrated in several reviews of placebo pharmacology.3,4 Patients tend to perceive larger capsules of placebo as being stronger than smaller ones, 2 placebo capsules as producing stronger effects than just 1,2 and injections as producing larger placebo effects than pills.3,4The literature on